The broad objective of this project is to determine the mechanisms by which the mammalian lung packages surfacant phospholipid for delivery to the alveolar subphase, the control mechanisms involved in this process, and relate these to oxidant injury and lung development. We have previously demonstrated that problems catalyzing the transfer of phospholipid between membranes (phospholipid exchange proteins) are involved in the lung surfacant system and that the transfer activities are altered during oxidant injury and lung development. The present proposal is designed to examine the mechanisms by which lung phospholipid exchange proteins control the packaging of phospholipids into lamellar bodies and to detect other proteins in the lung that may control surfacant phospholipid quantity and quality. The specific nature of the phospholipid exchange protein interaction with membranes and the role of membrane phospholipid and protein composition in modifying these interactions will be investigated. The activity of these proteins will be examined in lung development, in oxidant injury such as occurs in infants being treated for respiratory distress, and in normal and pathological human lung.